Assessment of unintentional weight loss

In most cases, unintentional weight loss is a subacute clinical problem. Patients who lose around 5% of their usual body weight over several months can usually receive an expedited outpatient work-up. However, several conditions are potentially life-threatening and may present with unintentional weight loss as a significant part of the clinical syndrome. Many of these conditions typically present with other characteristic signs and symptoms when fulminant; however, unintentional weight loss may be a prominent early feature.

Adrenal crisis

While adrenal insufficiency presents subacutely with fatigue, anorexia, weakness, orthostasis, and weight loss, adrenal crisis presents suddenly with hypotension and reduced organ perfusion and can be precipitated by a stress such as an infection. Acute abdominal pain has been reported. Primary adrenal insufficiency is more likely than secondary or tertiary adrenal insufficiency to present with adrenal crisis due to mineralocorticoid deficiency. Treatment requires immediate volume resuscitation and intravenous administration of either hydrocortisone or dexamethasone. Ideally, blood for laboratory studies should be drawn prior to glucocorticoid administration.

Thyroid storm

While hyperthyroidism is common and may present with unintentional weight loss, thyroid storm, the life-threatening manifestation of thyrotoxicosis, is rare. Patients may present with fever, altered mental status, tachyarrhythmia, and/or cardiac dysfunction causing hypotension and shock. It may also cause gastrointestinal symptoms. Resuscitation is targeted toward the presenting symptoms and includes management of the arrhythmia and any concomitant cardiac dysfunction, intravenous fluids and beta-blockers if not in decompensated heart failure, glucocorticoids, and treatments to block synthesis of the thyroid hormone. Patients are managed in an intensive care environment with input from endocrine consultants.

Diabetic ketoacidosis/hyperosmolar hyperglycaemic state

New-onset type 1 diabetes presents with subacute weight loss, polyuria, polydipsia, and malaise, but may also present emergently with diabetic ketoacidosis. Volume repletion and correction of electrolyte and acid-base abnormalities requires hospital care.[79]Diabetes UK.​ The management of diabetic ketoacidosis in adults*. Mar 2023 [internet publication]. https://www.diabetes.org.uk/professionals/resources/shared-practice/inpatient-and-hospital-care/joint-british-diabetes-society-for-inpatient-care

While type 1 diabetes more commonly presents with weight loss than type 2 diabetes, patients with type 2 diabetes may develop a subacute syndrome of severe hyperglycaemia (i.e., hyperosmolar hyperglycaemic state). Severe hyperglycaemia leads to glycosuria, caloric wasting, polyuria, polydipsia, and weight loss, and, in its most severe form, causes altered mental status and may progress to obtundation and coma.

Eating disorders

Patients with extreme starvation present with a severely low BMI and can have life-threatening bradycardia, hypothermia, hypotension, cardiomyopathy, and arrhythmia. Treatment is supportive and includes correcting electrolyte imbalances and careful restoration of body weight. Nutritional support must be provided carefully to prevent re-feeding syndrome (i.e., hypokalaemia, hypophosphataemia, thiamine deficiency, and heart failure associated with nutritional replacement). If the diagnosis is suspected but not known, other causes should be ruled out while psychiatric assessment is performed. Patients must be assessed for the risk of suicide.

Suicidal ideation

Psychiatric conditions associated with unintentional weight loss may also be associated with risk of suicide, including depression, bipolar disorder, and anorexia nervosa.

Life-threatening infections

Certain infections that are associated with subacute weight loss may require urgent evaluation, including infective endocarditis, pulmonary tuberculosis, and advanced HIV infection with opportunistic infection, as a delay in treatment would cause substantial morbidity.

Severe weight loss (any aetiology)

Severe diarrhoeal syndromes and malignancy may result in significant weight loss. Any patient with profound weakness or signs of organ failure may require hospitalisation to halt the loss of weight and restore organ function. Re-feeding syndrome should be monitored for carefully in these settings and a prompt work-up for underlying aetiology should be conducted.